CNS Drugs 2010; 24 (4): 319-326 ORIGINAL RESEARCH ARTICLE037 1172-7047/10/0004-0319/$49.95/0 252 2010 Adis Data Information BV. All rights reserved. For What Diagnoses Are Psychotropic Medications Being Prescribed? A Nationally Representative Survey of Physicians Tami L. Mark Thomson Reuters, Washington, DC, USA Abstract037 Background: Psychoactive medications, such as antidepressants, are one of the most widely prescribed categories of drugs in the US; yet few studies have comprehensively examined the conditions for which psychoactive medica tions are prescribed. To our knowledge, no prior study has examined the extent to which psychoactive medications are prescribed for non-psychiatric somatic illnesses or the main types of psychiatric disorders for which psychoactive medications are being used. Objective: To examine the diagnoses for which psychiatric medications are being prescribed in the US by analysing data from a nationally representative survey of physicians. Methods: The data were obtained from the 2005 National Disease and Therapeutic Index (NDTI), a continuing survey of a US office-based panel of physicians. The 2005 physician panel consisted of approximately 4000 phy sicians reporting quarterly, which was projected to a universe of 500 722 physicians. The study focused on the diagnoses that were given as the primary reason for prescribing the following types of psychotropic medications: anti depressants, antipsychotics and anti-anxiety medications. Results: Of the total number of antidepressant drug mentions, 92.7 % were prescribed for psychiatric conditions. The most common (65.3 %) were mood disorders (e.g. depression), followed by anxiety disorders (16.4%), which to gether comprised 81.7 % of all antidepressant drug mentions. Of the total number of anti-anxiety drug mentions, 67.7 % were prescribed for psychiatric conditions. The most common diagnosis was anxiety disorders (comprising 39.6 % of all drug mentions), followed by mood disorders (comprising 18.9 % of all drug mentions). Almost one-third of anxiety medication drug mentions were for non-psychiatric conditions or conditions of unspecified type. Of the total number of antipsychotic drug mentions, 98.9 % were prescribed for psychiatric conditions. The most common diagnoses, comprising 39.0 % of all drug mentions, were mood disorders such as depression and bipolar disorder. The second most common psychiatric diagnosis was schizophrenia or other psychotic disorders, comprising 34.5 % of drug mentions. Approximately 320 Mark 7.4% of drug mentions were for delirium, dementia, amnestic or other cog nitive disorders. Attention-deficit /conduct/disruptive behaviour disorders002 were the diagnoses indicated on 5.7% of all antipsychotic drug mentions.002 Anxiety disorders were indicated on 5.5% of antipsychotic drug mentions.002 Disorders usually diagnosed in infancy /childhood/adolescence (e.g. autism)002 comprised 2.3% of antipsychotic drug mentions.002 Conclusions: This research provides a broad view of the nature of psycho active medication prescribing, which may serve as a guide to future research,002 policy and education about these medications, their perceived benefits and002 risks, and their uses.002 Background Psychoactive medications, such as anti depressants, are one of the most widely pre scribed categories of drugs in the US.[1] Use of and spending on psychoactive medications in the US has grown rapidly over the past decade.[2] Analyses of spending from 1996 to 2001 found that about one-third of the increase in psychiatric prescription drug spending over that time period was due to more users and about two-thirds was from higher cost per user.[3] Despite the prevalence of psychoactive medica tion utilization, few studies have comprehensively examined the conditions for which psychoactive medications are prescribed. For example, to our knowledge, no prior study has examined the ex tent to which psychoactive medications are pre scribed for non-psychiatric somatic illnesses, such as pain. Further, as captured in the DSM IV[4] or the International Statistical Classification of Diseases and Related Health Problems-Ninth Revision-Clinical Modification ( ICD-9-CM),[5] psychiatric conditions are quite variable and span a number of syndromes and there are a variety of psychiatric conditions for which psychoactive medications can be prescribed. While off-label use of psychiatric medications has been docu mented, studies have not focused on which psychiatric conditions are being treated using the main classes of psychiatric medications. Data on the diagnoses for which medications are being prescribed are quite limited. The US Centers for Disease Control National Center for Health Statistics collects data on drug mentions through a survey of office-based physicians known as the National Ambulatory Medical Care Survey (NAMCS).[6] While this survey has been used to track psychoactive medication uti lization, it cannot be used to link prescriptions to diagnoses because the survey does not query physicians specifically about the diagnosis for which the medication was prescribed. Insurance claims data have also been used to understand psychoactive medication prescribing trends; however, prescription claims do not include diagnoses, and psychiatric diagnoses on medical claims that might help determine the reasons for psychoactive medication prescriptions are be lieved to be frequently under-coded. This study analysed data from a nationally representative survey of physicians to examine the diagnoses for which psychiatric medications are being prescribed in the US. The information is important for a variety of reasons, including iden tifying the need for research on new applications of existing medications, understanding off-label usage and informing possible labelling changes. Methods This study used data from the 2005 National Disease and Therapeutic Index (NDTI). The NDTI is a continuing survey of a US office-based panel of physicians conducted by IMS Health. The NDTI collects diagnostic and treatment data similar to that contained in the Center for Disease Control220s NAMCS. NDTI estimates were based 252 2010 Adis Data Information BV. All rights reserved. CNS Drugs 2010; 24 (4) 321 Diagnosis and Prescription of Psychotropic Medications on a universe of approximately 500 722 physicians that reside and practice within the continental USA. Physicians are recruited to participate in the NDTI survey from a sampling frame based on the American Medical Association and the American Osteopathic Association listings of all practising physicians. Approximately 4000 office- based, private practice physicians report per quarter. The sampling methodology employed was a two-stage, stratified, random sample. In the first stage, physicians were sampled. Two work days per month were subsampled from each doctor in the second stage. The sample was stratified by primary specialty and the nine census divisions. Physicians were recruited by telephone via a trained IMS recruiter. Approximately 34 physi cians were contacted for every one physician recruited into the sample. Physicians report on all patient contacts for two consecutive work days each quarter. Data are collected on approximately 2700 work days each month and 8000 work days each quarter. Information collected includes patient demo graphics, diagnosis and treatment information and physician demographics. The survey collects information through the use of a confidential log book in which physicians record information for each drug mention (i.e. each drug recommended or issued to a patient) and related diagnoses over a specified period. Each patient encounter can generate multiple diagnoses, and there is a direct correspondence between the recorded diagnosis and prescribed therapy. The 2005 sample is pro jected to a universe of physicians. The current study focused on drug mentions of the three main categories of psychotropic medications: antidepressants, antipsychotics and anti-anxiety medications. Antidepressants included tricyclics, tetracylics, monoamine oxidase (MAO) inhibitors, selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline (norepinephrine) reuptake inhibitors (SNRIs) and newer genera tion antidepressants. Anti-anxiety medications included benzodiazepines and other types of anti- anxiety drugs but excluded sedative hypnotics such as barbiturates. Antipsychotics included both first-(typical) and second-generation (atyp ical) antipsychotic medications. Diagnoses, coded using the ICD-9-CM, were grouped into psychiatric and non-psychiatric categories. Psychiatric diagnoses were defined as those of ICD-9-CM codes 290 205 314. Diagnoses were further grouped using the Clinical Classifi cations Software (CCS), a diagnosis and proce dure categorization that combines related codes from multiple chapters of the ICD-9-CM manual for policy analyses. CCS was developed as part of the Healthcare Cost and Utilization Project (HCUP), a Federal-State-Industry partnership sponsored by the Agency for Healthcare Re search and Quality.[7] Results Antidepressants were the most commonly prescribed of the three drug classes examined (with approximately 68 million drug mentions). Table I describes the diagnoses associated with antidepressant drug mentions. Of the total num ber of antidepressant drug mentions, 92.7 % were prescribed for psychiatric conditions. The most common (65.3 % ) were mood disorders (e.g. de pression), followed by anxiety disorders (16.4 % ), which together comprised 81.7 % of all anti depressant drug mentions. Antidepressants were also used for a variety of other psychiatric condi tions including at tention-deficit / conduct / disruptive behaviour disorders (2.8 % ), schizophrenia and other psychotic disorders (2.6 % ), adjustment dis orders (1.3 % ), delirium / dementia / amnestic / other cognitive disorders (1.0 % ), substance-related dis orders (0.3 % ) and others. Approximately 7.3 % of antidepressant prescriptions were prescribed for a variety of non-psychiatric diagnoses. About 1.1 % of antidepressant prescriptions were for head aches (including migraine). Another 1.0 % was prescribed for 217other connective tissue disease220 (e.g. fibromyalgia), and 0.8 % for 217other nervous system disorders220. About 0.8 % were for 217other female genital disorders220 (e.g. premenstrual ten sion) and about 0.7 % were for 217spondylosis; intervertebral disc disorders; other back problems220. Table II describes the diagnoses associated with the 21 million anti-anxiety medication drug mentions. Of the total number of drug mentions, 67.7 % were prescribed for psychiatric conditions. 252 2010 Adis Data Information BV. All rights reserved. CNS Drugs 2010; 24 (4) 322 Mark Table I. National estimates of antidepressants prescribed by office-based physicians by patient diagnosis categoriesa b Patient diagnoses Number of drug mentions (000) % of all antidepressant drug mentions (classified patient diagnoses except where stated otherwise) Total (classified or residual / unclassified)c Total classified c Psychiatric mood disorders anxiety disorders attention-deficit / conduct / disruptive behaviour disorders schizophrenia and other psychotic disorders adjustment disorders delirium / dementia / amnestic / other cognitive disorders miscellaneous mental disorders screening and history of mental health and substance abuse codes personality disorders substance-related disorders disorders usually diagnosed in infancy / childhood / adolescence impulse control disorders not elsewhere classified developmental disorders Non-psychiatric headache; including migraine other connective tissue disease other nervous system disorders other female genital disorders spondylosis: intervertebral disc disorders; other back problems other Residual/unclassified c 68 219 66 855 61 947 43 679 10 968 1 862 1 750 877 700 591 539 462 207 160 122 30 4 908 743 686 532 531 454 1 962 1 364 100.0 92.7 65.3 16.4 2.8 2.6 1.3 1.0 0.9 0.8 0.7 0.3 0.2 0.2 0.0 7.3 1.1 1.0 0.8 0.8 0.7 2.9 2.0d a Diagnosis categories are based on the CCS, Agency for Healthcare Research and Quality. b All entries, some of which are not strictly diagnoses, are based on International Statistical Classification of Diseases and Related Health Problems-Ninth Revision-Clinical Modification codes.[5] c According to CCS classification coding. d Represents percentage of total (classified or residual / unclassified) patient diagnoses. CCS = Clinical Classification Software. The most common diagnosis was anxiety dis orders (comprising 39.6 % of all drug mentions), followed by mood disorders (comprising 18.9% of all drug mentions). Almost one-third of anxiety medication drug mentions were for non- psychiatric conditions or conditions of unspecified type. In particular, 6 % of drug mentions were for 217medical examination / evaluation220 (e.g. V728: Specific Examination). Another 4.1 % of anxiety medications were prescribed for allergic reac tions, and 2.5 % for 217spondylosis; intervertebral disc disorders; other back problems220. Table III describes the diagnoses associated with the 18 800 antipsychotic medication drug mentions. Of the total number of antipsychotic drug mentions, 98.9 % were prescribed for psy chiatric conditions. The most common diag noses, comprising 39.0 % of all drug mentions, were mood disorders such as depression and bipolar disorder. The second most common psy chiatric diagnosis was schizophrenia or other psychotic disorders, comprising 34.5% of drug mentions. Approximately 7.4 % of drug mentions were for delirium, dementia, amnestic or other 252 2010 Adis Data Information BV. All rights reserved. CNS Drugs 2010; 24 (4) 323 Diagnosis and Prescription of Psychotropic Medications cognitive disorders. Attention-deficit / conduct / Anxiety disorders were indicated on 5.5 % of disruptive behaviour disorders were the diag-antipsychotic drug mentions. Disorders usually noses indicated on 5.7 % of all drug mentions. diagnosed in infancy / childhood / adolescence (e.g. Table II. National estimates of anti-anxiety medications prescribed by office-based physicians by patient diagnosis categoriesa b Patient diagnoses Number of drug mentions (000) % of all anti-anxiety drug mentions (classified patient diagnoses except where stated otherwise) Total (classified and residual / unclassified)c Total classifiedc Psychiatric Anxiety disorders Mood disorders Schizophrenia and other psychotic disorders Substance-related disorders Adjustment disorders Delirium / dementia / amnestic / other cognitive disorders Attention-deficit / conduct / disruptive behaviour disorders Personality disorders Miscellaneous mental disorders Impulse control disorders not elsewhere classified Developmental disorders Disorders usually diagnosed in infancy / childhood / adolescence Screening and history of mental health and substance abuse codes Non-psychiatric Medical examination / evaluation Allergic reactions Spondylosis; intervertebral disc disorders; other back problems Other aftercare Epilepsy; convulsions Gastrointestinal haemorrhage Sprains and strains Other inflammatory condition of skin Other skin disorders Headache; including migraine Other connective tissue disease Other and unspecified benign neoplasm Other hereditary and degenerative nervous system conditions Conditions associated with dizziness or vertigo Other Residual / unclassified c 20 983 20 407 13 810 8 089 3 851 422 393 305 241 170 159 61 54 29 18 18 6 597 1 227 831 516 268 251 233 188 176 169 168 165 130 101 98 2 076 576 100.0 67.7 39.6 18.9 2.1 1.9 1.5 1.2 0.8 0.8 0.3 0.3 0.1 0.1 0.1 32.3 6.0 4.1 2.5 1.3 1.2 1.1 0.9 0.9 0.8 0.8 0.8 0.6 0.5 0.5 10.2 2.75d a Diagnosis categories are based on the CCS, Agency for Healthcare Research and Quality. b All entries, some of which are not strictly diagnoses, are based on International Statistical Classification of Diseases and Related Health Problems-Ninth Revision-Clinical Modification codes.[5] c According to CCS classification coding. d Represents percentage of total (classified or residual / unclassified) patient diagnoses. CCS = Clinical Classification Software. 252 2010 Adis Data Information BV. All rights reserved. CNS Drugs 2010; 24 (4) 324 Mark Table III. National estimates of antipsychotic medications prescribed by office-based physicians by patient diagnosis categoriesa b Patient diagnoses Number of drug mentions (000) % of all antipsychotic drug mentions (classified patient diagnoses except where stated otherwise) Total (classified and residual / unclassified)c Total classified c Psychiatric Mood disorders Schizophrenia and other psychotic disorders Delirium / dementia / amnestic / other cognitive disorders Attention-deficit / conduct / disruptive behaviour disorders Anxiety disorders Disorders usually diagnosed in infancy / childhood / adolescence Personality disorders Impulse control disorders not elsewhere classified Substance-related disorders Developmental disorders Miscellaneous mental disorders Adjustment disorders Non-psychiatric Other hereditary and degenerative nervous system conditions Intracranial injury Other aftercare Diabetes mellitus with complications Nausea and vomiting Other nutritional, endocrine and metabolic disorders Other Residual / unclassified c 18 800 18 455 18 244d 7 195 6 368 1 369 1 046 1 019 426 268 223 130 86 79 36 211d 36 30 19 14 12 9 92 345 100.0 98.9 39.0 34.5 7.4 5.7 5.5 2.3 1.5 1.2 0.7 0.5 0.4 0.2 1.1 0.2 0.2 0.1 0.1 0.1 0.1 0.5 1.84e a Diagnosis categories are based on the CCS, Agency for Healthcare Research and Quality. b All entries, some of which are not strictly diagnoses, are based on International Statistical Classification of Diseases and Related Health Problems-Ninth Revision-Clinical Modification codes.[5] c According to CCS classification coding. d The difference from the sum total of individual drugs mentions is due to rounding. e Represents percentage of total (classified or residual / unclassified) patient diagnoses. CCS = Clinical Classification Software. autism) comprised 2.3 % of antipsychotic drug mentions. Discussion The data presented here on the types of diag noses for which psychiatric medications are being used have a number of implications. Using data from the 2001 NDTI, and examining the same drug classes as examined in this article (i.e. anti depressants, anxiolytics and antipsychotics), Radley and colleagues[8] estimated that approxi mately 31 % of the 18 million psychiatric drug mentions were for 217off-label220 diagnoses. Diagnoses were considered US FDA approved and 217on label220 if they could be matched to the therapeutic indications reported in the package insert of the drug. This study further informs the research by Radley and colleagues[8] concerning off-label usage by finding that about 99 % of antipsychotic medication drug mentions, 93 % of antidepressant drug mentions and 68 % of anti-anxiety medication drug mentions were for psychiatric conditions. Taken together, these two studies suggest that 252 2010 Adis Data Information BV. All rights reserved. CNS Drugs 2010; 24 (4) 325 Diagnosis and Prescription of Psychotropic Medications most off-label prescribing of psychiatric medica tions are for psychiatric conditions. This study also informs other current debates concerning psychoactive medication. For ex ample, there has been growing concern about the use of antipsychotics by children.[9] By the end of 2009, risperidone, aripiprazole, questiapine and olanzapine were approved for adolescents with schizophrenia and bipolar disorder. Risperidone and aripriprazole were also approved for treatment of irritability associated with autistic disorder. While this study does not include data on the age of those treated, it reveals that 5.7 % of anti- psychotic drug mentions or about 1 million drug mentions in 2005 were for attention-deficit / conduct / disruptive behaviour disorders, which are primarily paediatric diagnoses. Another 2.3 % of prescriptions, or about 426 000 drug mentions were for 217disorders usually diagnosed in in- fancy / childhood / adolescents220. These data suggest that more research and guidance is needed on the appropriateness, efficacy and safety of anti- psychotics in the treatment of attention-deficit hyperactivity disorder and conduct disorders. Another controversial usage of antipsychotic medications is for the treatment of dementia. The NDTI data revealed that in 2005, 7.4 % of anti- psychotic drug mentions or 1.4 million drug mentions were prescribed for 217delirium / dementia / amnestic / other cognitive disorders220. This was the third most common use of antipsychotic medi cation after mood disorders, and schizophrenia / other psychotic disorders. Recent research has revealed cerebrovascular risks and increased mortality associated with antipsychotic treat ment of elderly patients with dementia, which has led to warning labels on antipsychotic medica tions.[11,12] The use of antipsychotic medications for dementia may have declined since 2005 as a result of these warnings. This analysis found that 18.9 % of anti- anxiety medications were used to treat mood dis orders, rather than anxiety disorders, suggesting that more research may be helpful to further un derstand how anxiolytics are being used, and to inform physicians of the risks and benefits of anxiolytics in the treatment of unipolar and bipolar depression. For antidepressants, 0.3 % of the drug mentions, or 207 000 mentions, were for sub- stance-related disorders. Some research suggests that antidepressants may be effective in treating drug abuse[13-15] and alcoholism in certain genetic subtypes of alcoholic patients,[16,17] but this in formation has not been used in labelling. The study must be understood in light of its limitations. The diagnoses used were those recorded by physicians as the reason for the prescription. We cannot assess whether survey participation influenced the types of diagnoses recorded or types of medications prescribed. Additionally, medications were described as falling into three broad classes and the types of diagnoses for which medications were pre scribed may have varied within each class, for example, among first-and second-generation antipsychotics. Conclusions Psychotropic medications are one of the most commonly prescribed classes of drugs. With wide spread usage have come increased concerns that they are being used inappropriately, in populations that may not benefit, or that may be at heightened risk for adverse effects. Nevertheless, surprisingly little comprehensive information exists about the types of patient conditions that are being treated with psychotropic medication. The analyses pre sented here suggest that most prescribing of psychoactive medications is for psychiatric condi tions. However, the types of psychiatric conditions being treated are quite varied, highlighting the complexity and challenges of psychiatric diagnosis and treatment. The information presented in this study may serve as a guide to future research, policy and education about these medications, their perceived benefits and risks, and their uses. Acknowledgements This study was funded through a contract from the Sub stance Abuse and Mental Health Services Administration (SAMHSA) to Thomson Reuters. Jeffrey A. Buck, PhD, and Rita Vandivort-Warren MSW of SAMHSA, approved the study design, reviewed and commented on drafts of the manuscript and was involved in the decision to submit the 252 2010 Adis Data Information BV. All rights reserved. CNS Drugs 2010; 24 (4) 326 Mark st udy to this journal. The views expressed here do not ne cessarily reflect those of SAMHSA or the US Department of Health and Human Services. Katharine Levit and Cheryl Kassed, PhD, of Thomson Reuters, commented on drafts of the manuscript and provided editorial assistance. Staff at IMS Health reviewed the data tables for accuracy. The author of the manuscript is a salaried employee of Thomson Reuters. Thomson Reuters provides analytic consulting to a variety of clients involved in the healthcare industry including the US Federal government, state governments, the pharmaceutical industry, hospitals, physicians and others. References 1. Lamb E. Top 200 prescription drugs of 2006 [online]. Avail able from URL: http://wwwpharmacytimescom/issue/phar macy/2007/2007-05/2007-05-6472 [Accessed 2009 Jun 19] 2. Mark TL, Levit KR, Buck JA, et al. Mental health treatment expenditure trends, 1986-2003. Psychiatr Serv 2007 Aug; 58 (8): 1041-8 3. Zuvekas SH. Prescription drugs and the changing patterns of treatment for mental disorders, 1996-2001. Health Aff (Millwood) 2005 Jan-Feb; 24 (1): 195-205 4. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994 5. International Classification of Diseases, Version 9, Clinical Modification (ICD-9-CM). Washington, DC: Health and Human Services Department, Centers for Disease Control and Prevention, Centers for Medicare and Medicaid Ser vices, 2009 6. Centers for Disease Control and Prevention National Center for Health Statistics. National Ambulatory Medical Care Survey 2005 [online]. Available from URL: http://www. cdc.gov/nchs/ahcd/ahcd_questionnaires.htm [Accessed 2009 Aug 10] 7. Elixhauser A, Steiner CA, Whittington C. Clinical classifi cations for health policy research: hospital inpatient statis tics, 1995 [online]. Healthcare Cost and Utilization Project, HCUP 3 Research Note. Rockville (MD): Agency for Health Care Policy and Research, 1998: AHCPR Pub. No. 98-0049. Available from URL: http://www.hcup-us.ahrq. gov/reports/natstats/his95.htm [Accessed 2009 Jun 19] 8. Radley DC, Finkelstein SN, Stafford RS. Off-label pre scribing among office-based physicians. Arch Intern Med 2006 May 8; 166 (9): 1021-6 9. Rosak J. AMA calls for studies of psychotropic use in chil dren: psychiatric news 2001 [online]. Available from URL: http://pnpsychiatryonlineorg/cgi/content/full/36/2/2 [Ac cessed 2009 Jun 19] 10. Health Day (Medline Plus). FDA panel OKs newer anti- psychotics for children [online]. Available from URL: http://www.nlm.nih.gov/medlineplus/news/fullstory_85467. html [Accessed 2009 Jun 19] 11. Salzman C, Jeste DV, Meyer RE, et al. Elderly patients with dementia-related symptoms of severe agitation and ag gression: consensus statement on treatment options, clin ical trials methodology, and policy. J Clin Psychiatry 2008 Jun; 69 (6): 889-98 12. Ballard C, Hanney ML, Theodoulou M, et al. The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial. Lancet Neurol 2009 Feb; 8 (2): 151-7 13. Elkashef AM, Rawson RA, Anderson AL, et al. Bupropion for the treatment of methamphetamine dependence. Neuro psychopharmacology 2008 Apr; 33 (5): 1162-70 14. Elkashef A, Vocci F, Huestis M, et al. Marijuana neuro biology and treatment. Subst Abuse 2008; 29 (3): 17-29 15. Dwoskin LP, Rauhut AS, King-Pospisil KA, et al. Review of the pharmacology and clinical profile of bupropion, an antidepressant and tobacco use cessation agent. CNS Drug Rev 2006 Fall-Winter; 12 (3-4): 178-207 16. Nellissery M, Feinn RS, Covault J, et al. Alleles of a func tional serotonin transporter promoter polymorphism are associated with major depression in alcoholics. Alcohol Clin Exp Res 2003 Sep; 27 (9): 1402-8 17. Pettinati HM, Volpicelli JR, Kranzler HR, et al. Sertraline treatment for alcohol dependence: interactive effects of medication and alcoholic subtype. Alcohol Clin Exp Res 2000 Jul; 24 (7): 1041-9 Correspondence: Dr Tami L. Mark , Director, Thomson037 Reuters, 4301 Connecticut Avenue, Suite 330, Washington,037 DC 20008, USA.037 E-mail: Tami.mark@thomsonreuters.com037 252 2010 Adis Data Information BV. All rights reserved. CNS Drugs 2010; 24 (4)